Therapeutic Potential of the Endocannabinoid System in the Brain

Abstract

Cannabinoids have been predominantly considered as the substances responsible of the psychoactive properties of marijuana and other derivatives of Cannabis sativa. However, these compounds are now being also considered for their therapeutic potential, since the term "cannabinoid" includes much more compounds than those present in Cannabis sativa derivatives. Among them, there are numerous synthetic cannabinoids obtained by modifications from plant-derived cannabinoids, but also from the compounds that behave as endogenous ligands for the different cannabinoid receptor subtypes. Within the family of "cannabinoid-related compounds", one should also include some prototypes of selective antagonists for these receptors, and also the recently developed inhibitors of the mechanism of finalization of the biological action of endocannabinoids (transporter + FAAH). All this boom of the cannabinoid pharmacology has, therefore, an explanation in the recent discovery and characterization of the endocannabinoid signaling system, which plays a modulatory role mainly in the brain but also in the periphery. The objective of the present article will be to review, from pharmacological and biochemical points of view, the more recent advances in the study of the endocannabinoid system and their functions in the brain, as well as their alterations in a variety of pathologies and the proposed therapeutic benefits of novel cannabinoid-related compounds that improve the pharmacokinetic and pharmacodynamic properties of classic cannabinoids.

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…Neurotoxicity and Neurotrauma. The endocannabinoid system plays an important role in neuroprotection both in acute neuronal injury (e.g., traumatic brain injury, stroke, and epilepsy) and in chronic neurodegenerative disorders, such as multiple sclerosis, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease (reviewed in Glass, 2001;Mechoulam et al, 2002a,b;Grundy, 2002;Croxford, 2003;Drysdale and Platt, 2003;Jackson et al, 2005a;Ramos et al, 2005). Although the underlying mechanisms are not fully understood, multiple cannabinoid receptor-dependent as well as receptor-independent processes have been implicated.…”

Cannabis for Inflammatory Bowel Disease

“…Endocannabinoids also play a peripheral modulatory role affecting the immune and cardiovascular systems, as well as reproductive endocrine processes and control of energy metabolism [6]. Anandamide is able to produce analgesia, control motor activity, reduce emesis, stimulate appetite, and induce hypothermia.…”

Toward the design of cannabinoid CB1 receptor inverse agonists and neutral antagonists

“…Many excellent recent reviews have considered the therapeutic utilities of cannabinoid agonists, antagonists and inverse agonists [Cervino et al, 2007;Jonsson et al, 2006;Makriyannis et al, 2005;Pertwee, 2005b;Ramos et al, 2005]. The major therapeutic use for cannabinoid inverse agonists/antagonists has centered on the treatment of metabolic syndrome and obesity [Antel et al, 2006;Cervino et al, 2007] [Jagerovic et al, 2008].…”